The proposed work continues a long-standing investigation of the mechanism of radiation-induced mutagenesis in Escherichia coli. The current phase of this project centers on the hypothesis that ultraviolet light (UV), as well as other mutagenic and carcinogenic agents, induce the coordinated derepression of a cluster of survival-promoting functions not normally synthesized in healthy cells. Damage to DNA serves as the regulatory signal which triggers multiple derepression of UV-inducible functions, one of which is an error-prone type of DNA repair (SOS repair) now believed to be responsible for UV mutagenesis and for the major part of X-ray mutagenesis as well. Recent work on this project, and in a few other laboratories, strongly implicates an inducible DNA polymerase which is capable of inserting bases by random end-addition in regions of the DNA containing non-coding lesions (such as pyrimidine dimers) in the template strand. Work during the coming year on this project will center on mutant strains of E. coli B/r in which different members of the inducible clusters of UV-inducible functions are abolished, or altered in their quantitative expression, in a variety of distinct patterns. Some of these mutations map in the laxA region and may be intragenic suppressors of the lexA mutant phenotype (i.e., inability to express any of the dozen or more known UV-inducible funtions, which require wild type lexA ion and recA ion gene products for normal expression of the entire cluster). Others (and our effort during this phase of the project will be directed primarily toward these) map in several different locations outside both recA and lexA, and exert a multiplicity of differential effects on the pattern of expression of individual UV-inducible functions. Our investigation of these mutations will include extensive mapping of the mutations, characterization of as many different pleiotropic patterns of expression as possible, and the construction of testable hypotheses to interpret the effects observed. BIBLIOGRAPHIC REFERENCES: Witkin, E.M. Elevated mutability of polA and uvrA polA derivatives of Escherichia coli B/r at sublethal doses of ultraviolet light: evidence for an inducible error-prone repair system ("SOS repair") and its anolalous expression in these strains. Genetics 79 suppl.:199-213, 1975. George, D.L. (Text Truncated - Exceeds Capacity)